Although epigenetic modifications undoubtedly serve as an important regulatory mechanism during CD4+ T cell fate choice, there is a paucity of information related to the epigenetic changes that occur during differentiation. Moreover, previous studies on epigenetic modifications of signature cytokine loci and the Foxp3 locus focused mainly on conserved noncoding sequences (CNS) further limiting the view of critical chromatin structures that maintain the lineage commitment.we have used the high-throughput ChIP-Seq approach to generate genome-wide H3K4me3 and H3K27me3 maps in nave, Th1, Th2, Th17, iTreg, and nTreg cells to gain insights into lineage commitment and plasticity in developing T cells. Our results point to surprising complexity in the potential regulation of transcription factors, cytokines, chemokines and receptors that contribute to the phenotype considered as Th cell lineages. We found that although modifications of signature cytokine genes (Ifng, Il4, and Il17) partially conform to the expectation of lineage commitment, critical transcription factors such as Tbx21 exhibit a broad spectrum of epigenetic states, consistent with our demonstration of T-bet and IFN-? induction in nTreg cells. Our data suggest an epigenetic mechanism underlying the specificity and plasticity of effector and regulatory T cells and also provide a framework for understanding complexity of CD4+ T helper cell differentiation.